Multicenter phase II study of nivolumab in Japanese patients with relapsed or refractory classical Hodgkin lymphoma

Abstract

Overexpression of programmed death‐1 (PD‐1) ligands contributes to an immunosuppressive microenvironment. Nivolumab is a PD‐1‐blocking antibody that inhibits the PD‐1 pathway and showed good efficacy in several types of malignancy. This phase II study examined the efficacy and safety of nivolumab in 17 Japanese patients with refractory/relapsed classical Hodgkin lymphoma previously treated with brentuximab vedotin. Sixteen patients were included in efficacy analyses and 17 in safety analyses. The primary endpoint was the centrally assessed objective response rate (ORR). The study was commenced in March 2015. We report data obtained at a cutoff of 16 March 2016, at which time 11 patients were still receiving nivolumab. The median (range) duration of treatment and follow‐up were 7.0 (1.4–10.6) months and 9.8 (6.0–11.1) months, respectively. All 17 patients had previously received brentuximab vedotin. The ORR was 81.3% (95% confidence interval [CI]: 54.4–96.0%; 13/16 patients), with complete remission and partial remission in 4 and 9 patients, respectively. The overall survival (OS) and progression‐free survival (PFS) rates at 6 months were 100 and 60.0% (95% CI: 31.8–79.7%), respectively; the median OS and PFS were not reached. The most common adverse events (AE) were pyrexia (41.2%), pruritus (35.3%), rash (35.3%) and hypothyroidism (29.4%). Four patients (23.5%) experienced grade 3 or 4 AE, but most AE were of grade 1 or 2. In conclusion, nivolumab is a potentially effective and tolerable treatment option for Japanese patients with relapsed/refractory classical Hodgkin lymphoma previously treated with brentuximab vedotin.

Risk factors for cancer-associated thrombosis in patients undergoing treatment with immune checkpoint inhibitors

“…On comparing standard antineoplastic therapy used with or without Bev, VTE onset rate was reported to be 1.33 times higher in the Bev group than in the non-Bev group [12]. In the case of nivolumab administration, only VTE incidence [13][14][15][16][17][18][19][20] has been reported and no reports on risk factors for CAT onset including ATE are present. Moreover, no reports on VTE or ATE onset rate during pembrolizumab administration are available.…”

Treatment of relapsed or refractory classical Hodgkin lymphoma with the anti-PD-1, tislelizumab: results of a phase 2, single-arm, multicenter study

“…Somatic alterations in MHC class I or II expression have shown correlation with response to PD-1 inhibition [33,34], and underlying human leukocyte antigen variability has also been suggested to impact outcome [35]. Studies of other PD-1 inhibitors in patients with cHL in China [31] and Japan [36] have not shown the depth of responses observed in the current trial, however, arguing against race being a major determinant of response. Nonetheless, more in-depth studies of potential ethnic or geographic determinants of response are warranted.…”

Stop and go: hematopoietic cell transplantation in the era of chimeric antigen receptor T cells and checkpoint inhibitors

“…Responses were in general durable. Subsequent studies with Nivolumab in recurrent HL confirmed high ORRs ranging from 66.3-81.3%, without excessive toxicity (40, 41). Similar results were seen with a second anti-PD-1 antibody, Pembrolizumab (42) (43).…”